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Animal Models of Multiple Sclerosis available through NDI
Primate model
Our primate model is the marmoset, inoculated with whole human myelin. The principal endpoint is behavioral, with repeated measuring up to 3 or 4 months following disease induction, depending on the experimental design (prevention or treatment after onset of symptoms). The principal investigator for this model is the person who developed it. In addition to behavioral endpoints, there can also be imaging (MRI, for quantification of lesion volume), immunological (T cell reactivity, PBL's, splenocytes) and histopathological (inflammation and demyelination quantification) endpoints. The model is considered to provide more information on the range of effects of a test compound compared to rodent models.
Rodent models
The following rat and mouse models of MS reflect varying aspects of the disease, including the two primary clinical forms of the disease, acute and relapsing/remitting.
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Lewis rat acute experimental autoimmune encephalopathy (EAE), induced with spinal cord or myelin basic protein.
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Lewis rat adoptive EAE induced with myelin basic protein.
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SJL mouse chronic EAE induced with proteolipid protein.
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Biozzi mouse chronic relapsing EAE induced with lyophilised spinal cord.
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Experimental autoimmune uveoretinitis in the B10.RIII mouse.
With these rodent models pK studies can be incorporated into the study design. In addition, lymphocyte transformation studies can be undertaken in parallel to determine drug actions on components of the immune system involved in the development of autoimmunity.
With the rat models, a unique assay is also possible: in vivo cell tracking of macrophage brain infiltration by Magnetic Resonance Imaging (MRI), using ultra-small superparamagentic iron oxide (USPIO). Details of this assay are summarized below. What this assay allows is early and accurate predictions of which specific animals will develop the disorder, and how severe it will be, following experimental induction of encephalomyelitis. These animals can then be used for testing the efficacy of various therapeutics. This novel pre-clinical approach using the EAE model is now being used in clinical trials.
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Macrophage Tracking In Vivo
The macrophage cell tracking approach is applied during the first clinical signs of MS. Potential therapies are then administered, and their efficacy monitored in vivo by MRI, which reveals the suppression of monocyte/macrophage brain infiltration. These in vivo observations are then followed by histopathology and immunohistochemistry, to confirm the extent of CNS inflammation (macrophages, T cells), demyelination, axonal damage and permanent axonal loss (see, for example: Boullerne et al., Anti-S-nitrosocysteine antibodies are a predictive marker for demyelination in experimental autoimmune encephalomyelitis: implications for multiple sclerosis. J Neurosci. 2002 [22]: 123-132.) |
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